Background: In oncology, progression-free survival (PFS) is a surrogate outcome
measure and trial end point, which is increasingly being used to determine the efficacy
and implementation in patient care of new drugs. The goal of patient-centred cancer care
is to extend overall survival (OS) or improve health-related quality of life (HRQoL),
however, drugs with PFS benefit are more commonly being approved for use in the
absence of OS, when patient benefit would have to arise from improved HRQoL. The
association between PFS and HRQoL in oncology has been poorly studied, and this
association remains unknown. The objective of this thesis was to thoroughly evaluate the
PFS-HRQoL association in oncology.
Methods: We published a protocol outlining the design of a highly comprehensive
systematic review, and a new analytical approach to optimally explore the PFS-HRQoL
association from published oncology randomized controlled trials (RCTs). We recruited
an international team of reviewers to conduct the systematic review across three HRQoL
domains, and performed a quantitative analysis to find the PFS-HRQoL association in
oncology. We examined our database of eligible RCTs for methodological issues through
a descriptive exploration of risk of bias, to further inform on the design and conduct of
future RCTs.
Results: We failed to find an association between PFS and HRQoL in the absence of OS
in oncology. Very few published oncology RCTs measure and report HRQoL
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information, and among those that do, design and conduct issues related to blinding, and
especially attrition are common.
Conclusion: Oncology RCTs must either be adequately powered for OS, or designed to
properly measure HRQoL, so patients can receive treatments offering benefit in one of
these two patient-centered outcomes, and not solely based on PFS. There is a lack of high
quality RCTs informing on the PFS-HRQoL association, and more of these types of trials
are needed in the future for further analysis to confirm our findings.